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Discoid lupus erythematosus (DLE) is a common autoimmune skin disease in dogs. Conventional treatments, such as corticosteroids, can be effective but often have side effects. This case report presents a successful use of cannabinoid therapy (CT) in a dog with DLE resistant to conventional treatment. A 2-year-old mixed-breed dog with a history of DLE presented with worsening lesions despite treatment with corticosteroids and other medications. Liver enzymes levels were elevated, indicating corticosteroid-induced side effects. CT with a CBD-rich full spectrum Cannabis oil was initiated. The dosage was gradually adjusted until the minimum effective dose was found. Within a few weeks of starting CT, the dog showed significant improvement in skin lesions and in liver enzymes levels. After 1 year, the dog remains clinically stable on a low dose of full-spectrum CBD-rich oil. No evidence of DLE recurrence was observed. This case suggests that CT may be a viable alternative or complementary therapy for DLE in dogs, particularly for those experiencing adverse effects from conventional treatments. Further research is warranted to confirm the efficacy and safety of CT for DLE management in dogs.

Discoid lupus erythematosus (DLE) is a common autoimmune skin disease in dogs. Conventional treatments, such as corticosteroids, can be effective but often have side effects. This case report presents a successful use of cannabinoid therapy (CT) in a dog with DLE resistant to conventional treatment. A 2-year-old mixed-breed dog with a history of DLE presented with worsening lesions despite treatment with corticosteroids and other medications. Liver enzymes levels were elevated, indicating corticosteroid-induced side effects. CT with a CBD-rich full spectrum Cannabis oil was initiated. The dosage was gradually adjusted until the minimum effective dose was found. Within a few weeks of starting CT, the dog showed significant improvement in skin lesions and in liver enzymes levels. After 1 year, the dog remains clinically stable on a low dose of full-spectrum CBD-rich oil. No evidence of DLE recurrence was observed. This case suggests that CT may be a viable alternative or complementary therapy for DLE in dogs, particularly for those experiencing adverse effects from conventional treatments. Further research is warranted to confirm the efficacy and safety of CT for DLE management in dogs. [ABSTRACT FROM AUTHOR]

Background: Transmissible venereal tumour (TVT), also called Sticker Tumour, is a round cell tumour whose transmission occurs mainly through sexual contact between animals or direct transplantation of the neoplastic cell through licking or through direct contact with the lesioned area. TVT is the most common tumor found in stray dogs and predominantly affects the genital area and, in case of bitches, occurs in the vagina and foreskin, as well as the oral and nasal cavities. Intracavitary TVT is rarely reported. The aim of this paper is to report a case of an old neutered bitch affected by vaginal and intracavitary TVT, treated at the Veterinary School Clinic (CVE) of the Federal University of Santa Catarina (UFSC), Curitibanos campus, Brazil. Case: An approximately 10-year-old mixed breed bitch, weighing 18,5 kg and, neutered 2 years previously at the same institution, was brought by her owner, who reported dyskinesia, constipation, and serosanguinous vaginal discharge for a few weeks. Physical examination showed a row of 4 smooth, round masses with a soft consistency ranging from 1 to 2 cm at the bottom of the vaginal roof. The patient was referred for an ultrasound (US) and a vaginal swab was taken for cytological examination, whose result demonstrated TVT. The result of the US scan showed a heterogeneously shaped structure, with a more hypoechogenic center in relation to the periphery and irregular contours, measuring around 2.63 x 6.10 cm, in the uterine topography caudally to the bladder. Exploratory laparotomy was performed with total removal of the mass, which was surrounding the proximal urethra, and the material was sent for histological and cytological analysis, whose both results indicated TVT. Chemotherapy was then initiated, with 6 intravenous administrations of vincristine (0.5 mg/m2) with an interval of 15 days between each administration. The animal underwent a total of 6 chemotherapy sessions, without complete improvement of the vaginal tumours. A 2nd chemotherapy protocol based on doxorubicin was suggested, which was not accepted by the owner. Three months after the end of the original chemotherapy protocol, the patient was assessed again and it was found that there had been no progression of the vaginal masses on vaginal palpation and no signs of recurrence of the intracavitary mass on ultrasound. Discussion: TVT is a venereal tumor that affects almost 100% of non-neutered animals, males and females. In the case of bitches, the most common sites are the vagina (53%), vulva (13%) and extragenital areas (14%). This animal had no intracavitary mass at the time of her castration 2 years earlier. At the time of diagnosis, she had the extragenital form of the tumor, consisting of an intra-abdominal mass, in addition to the genital masses in the vaginal roof. The chemotherapy drug vincristine is the drug of choice for the treatment of transmissible venereal tumors, due to its high efficacy associated with 4 to 6 sessions. However, in this case, there was no total improvement, so it was classified as a case of proven pharmacological resistance as the chemotherapy was ineffective for the complete regression of the tumor. It was therefore concluded that the occurrence of intracavitary TVTs, although rare, warrants a thorough physical examination combined with diagnostic tools such as ultrasound and histology, even in castrated old patients. [ABSTRACT FROM AUTHOR]

Platinosomosis is a systemic parasitic disease with a hepatic predilection caused by the trematode Platynosomum spp. It occurs mainly in felines through ingestion of the paratenic host, or from a second intermediate host, which would be terrestrial isopods in endemic tropical areas around the world. The pathophysiology includes cases of hepatic lipidosis, cholangitis and cholangiohepatitis, with their severity related to the level of parasite load in the final host. The present work aims to report two cases of feline platinosomosis seen at the Clinical Veterinary School (CVE) of the Federal University of Santa Catarina (UFSC), in Curitibanos, SC. Both cases correspond to two domiciled female felines aged six to eight months with complaints of emesis and hematochezia. Furthermore, one of the animals had diarrhea and the other had pasty feces, both with a history of delayed vaccinations and deworming. Laboratory tests showed thrombocytopenia, changes in ALT, GGT and FA enzymes, abdominal ultrasound demonstrated a small thickening of the gastric wall and fecal parasitology showed a positive result for the presence of the species of Platynosomum fastosum (= P. illiciens) in fecal samples. The present work consists of the report of the first two cases described in the central region of the Santa Catarina highland, with the disease previously described only in the municipality of Araquari, in the north of the state. [ABSTRACT FROM AUTHOR]

The seamless transition through stages of pluripotency relies on a balance between transcription factor networks and epigenetic mechanisms. Here, we reveal the crucial role of the transgene activation suppressor (TASOR), a component of the human silencing hub (HUSH) complex, in maintaining cell viability during the transition from naive to primed pluripotency. TASOR loss in naive pluripotent stem cells (PSCs) triggers replication stress, disrupts H3K9me3 heterochromatin, and impairs silencing of LINE-1 (L1) transposable elements, with more severe effects in primed PSCs. Notably, the survival of Tasor knockout PSCs during this transition can be restored by inhibiting caspase or deleting the mitochondrial antiviral signaling protein (MAVS). This suggests that unscheduled L1 expression activates an innate immune response, leading to cell death specifically in cells exiting naive pluripotency. Our findings highlight the importance of epigenetic programs established in naive pluripotency for normal development., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The zebrafish Danio rerio has become a popular model host to explore disease pathology caused by infectious agents. A main advantage is its transparency at an early age, which enables live imaging of infection dynamics. While multispecies infections are common in patients, the zebrafish model is rarely used to study them, although the model would be ideal for investigating pathogen-pathogen and pathogen-host interactions. This may be due to the absence of an established multispecies infection protocol for a defined organ and the lack of suitable image analysis pipelines for automated image processing. To address these issues, we developed a protocol for establishing and tracking single and multispecies bacterial infections in the inner ear structure (otic vesicle) of the zebrafish by imaging. Subsequently, we generated an image analysis pipeline that involved deep learning for the automated segmentation of the otic vesicle, and scripts for quantifying pathogen frequencies through fluorescence intensity measures. We used Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae, three of the difficult-to-treat ESKAPE pathogens, to show that our infection protocol and image analysis pipeline work both for single pathogens and pairwise pathogen combinations. Thus, our protocols provide a comprehensive toolbox for studying single and multispecies infections in real-time in zebrafish., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Schmitz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

How to derive principles of community dynamics and stability is a central question in microbial ecology. Bottom-up experiments, in which a small number of bacterial species are mixed, have become popular to address it. However, experimental setups are typically limited because co-culture experiments are labor-intensive and species are difficult to distinguish. Here, we use a four-species bacterial community to show that information from monoculture growth and inhibitory effects induced by secreted compounds can be combined to predict the competitive rank order in the community. Specifically, integrative monoculture growth parameters allow building a preliminary competitive rank order, which is then adjusted using inhibitory effects from supernatant assays. While our procedure worked for two different media, we observed differences in species rank orders between media. We then parameterized computer simulations with our empirical data to show that higher order species interactions largely follow the dynamics predicted from pairwise interactions with one important exception. The impact of inhibitory compounds was reduced in higher order communities because their negative effects were spread across multiple target species. Altogether, we formulated three simple rules of how monoculture growth and supernatant assay data can be combined to establish a competitive species rank order in an experimental four-species community., Competing Interests: The authors declare that they have no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)

Many neurodevelopmental defects are linked to perturbations in genes involved in housekeeping functions, such as those encoding ribosome biogenesis factors. However, how reductions in ribosome biogenesis can result in tissue and developmental specific defects remains a mystery. Here we describe new allelic variants in the ribosome biogenesis factor AIRIM primarily associated with neurodevelopmental disorders. Using human cerebral organoids in combination with proteomic analysis, single-cell transcriptome analysis across multiple developmental stages, and single organoid translatome analysis, we identify a previously unappreciated mechanism linking changes in ribosome levels and the timing of cell fate specification during early brain development. We find ribosome levels decrease during neuroepithelial differentiation, making differentiating cells particularly vulnerable to perturbations in ribosome biogenesis during this time. Reduced ribosome availability more profoundly impacts the translation of specific transcripts, disrupting both survival and cell fate commitment of transitioning neuroepithelia. Enhancing mTOR activity by both genetic and pharmacologic approaches ameliorates the growth and developmental defects associated with intellectual disability linked variants, identifying potential treatment options for specific brain ribosomopathies. This work reveals the cellular and molecular origins of protein synthesis defect-related disorders of human brain development., Highlights: AIRIM variants reduce ribosome levels specifically in neural progenitor cells. Inappropriately low ribosome levels cause a transient delay in radial glia fate commitment.Reduced ribosome levels impair translation of a selected subset of mRNAs.Genetic and pharmacologic activation of mTORC1 suppresses AIRIM-linked phenotypes.

Embryogenesis necessitates harmonious coordination between embryonic and extraembryonic tissues. Although stem cells of both embryonic and extraembryonic origins have been generated, they are grown in different culture conditions. In this study, utilizing a unified culture condition that activates the FGF, TGF-β, and WNT pathways, we have successfully derived embryonic stem cells (FTW-ESCs), extraembryonic endoderm stem cells (FTW-XENs), and trophoblast stem cells (FTW-TSCs) from the three foundational tissues of mouse and cynomolgus monkey (Macaca fascicularis) blastocysts. This approach facilitates the co-culture of embryonic and extraembryonic stem cells, revealing a growth inhibition effect exerted by extraembryonic endoderm cells on pluripotent cells, partially through extracellular matrix signaling. Additionally, our cross-species analysis identified both shared and unique transcription factors and pathways regulating FTW-XENs. The embryonic and extraembryonic stem cell co-culture strategy offers promising avenues for developing more faithful embryo models and devising more developmentally pertinent differentiation protocols., Competing Interests: Declaration of interests Y.W., L.Y., T.T., and J.W. are inventors on a patent application (applied through the Board of Regents of The University of Texas System, application number 63/488,401) entitled “Methods For the Derivation Culture Of Embryonic and Extra-Embryonic Stem Cells” arising from this work., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Bacterial infections are often polymicrobial, leading to intricate pathogen-pathogen and pathogen-host interactions. There is increasing interest in studying the molecular basis of pathogen interactions and how such mechanisms impact host morbidity. However, much less is known about the ecological dynamics between pathogens and how they affect virulence and host survival. Here we address these open issues by co-infecting larvae of the insect model host Galleria mellonella with one, two, three or four bacterial species, all of which are opportunistic human pathogens. We found that host mortality was always determined by the most virulent species regardless of the number of species and pathogen combinations injected. In certain combinations, the more virulent pathogen simply outgrew the less virulent pathogen. In other combinations, we found evidence for negative interactions between pathogens inside the host, whereby the more virulent pathogen typically won a competition. Taken together, our findings reveal positive associations between a pathogen's growth inside the host, its competitiveness towards other pathogens and its virulence. Beyond being generalizable across species combinations, our findings predict that treatments against polymicrobial infections should first target the most virulent species to reduce host morbidity, a prediction we validated experimentally.

Faithful embryogenesis requires precise coordination between embryonic and extraembryonic tissues. Although stem cells from embryonic and extraembryonic origins have been generated for several mammalian species(Bogliotti et al., 2018; Choi et al., 2019; Cui et al., 2019; Evans and Kaufman, 1981; Kunath et al., 2005; Li et al., 2008; Martin, 1981; Okae et al., 2018; Tanaka et al., 1998; Thomson et al., 1998; Vandevoort et al., 2007; Vilarino et al., 2020; Yu et al., 2021b; Zhong et al., 2018), they are grown in different culture conditions with diverse media composition, which makes it difficult to study cross-lineage communication. Here, by using the same culture condition that activates FGF, TGF-β and WNT signaling pathways, we derived stable embryonic stem cells (ESCs), extraembryonic endoderm stem cells (XENs) and trophoblast stem cells (TSCs) from all three founding tissues of mouse and cynomolgus monkey blastocysts. This allowed us to establish embryonic and extraembryonic stem cell co-cultures to dissect lineage crosstalk during early mammalian development. Co-cultures of ESCs and XENs uncovered a conserved and previously unrecognized growth inhibition of pluripotent cells by extraembryonic endoderm cells, which is in part mediated through extracellular matrix signaling. Our study unveils a more universal state of stem cell self-renewal stabilized by activation, as opposed to inhibition, of developmental signaling pathways. The embryonic and extraembryonic stem cell co-culture strategy developed here will open new avenues for creating more faithful embryo models and developing more developmentally relevant differentiation protocols., Competing Interests: DECLARATION OF INTERESTS Y.W., L.Y., T.T. and J.W. are inventors on a patent application (applied through the Board of Regents of The University of Texas System, application number 63/488,401) entitled “Methods For the Derivation Culture Of Embryonic and Extra-Embryonic Stem Cells” arising from this work. The other authors declare no competing interests.

Our understanding of human early development is severely hampered by limited access to embryonic tissues. Due to their close evolutionary relationship with humans, nonhuman primates are often used as surrogates to understand human development but currently suffer from a lack of in vivo datasets, especially from gastrulation to early organogenesis during which the major embryonic cell types are dynamically specified. To fill this gap, we collected six Carnegie stage 8-11 cynomolgus monkey (Macaca fascicularis) embryos and performed in-depth transcriptomic analyses of 56,636 single cells. Our analyses show transcriptomic features of major perigastrulation cell types, which help shed light on morphogenetic events including primitive streak development, somitogenesis, gut tube formation, neural tube patterning and neural crest differentiation in primates. In addition, comparative analyses with mouse embryos and human embryoids uncovered conserved and divergent features of perigastrulation development across species-for example, species-specific dependency on Hippo signalling during presomitic mesoderm differentiation-and provide an initial assessment of relevant stem cell models of human early organogenesis. This comprehensive single-cell transcriptome atlas not only fills the knowledge gap in the nonhuman primate research field but also serves as an invaluable resource for understanding human embryogenesis and developmental disorders., (© 2022. The Author(s).)

Although features of ribosome assembly are shared between species, our understanding of the diversity, complexity, dynamics, and regulation of ribosome production in multicellular organisms remains incomplete. To gain insights into ribosome biogenesis in human cells, we perform a genome-wide loss-of-function screen combined with differential labeling of pre-existing and newly assembled ribosomes. These efforts identify two functionally uncharacterized genes, C1orf109 and SPATA5. We provide evidence that these factors, together with CINP and SPATA5L1, control a late step of human pre-60S maturation in the cytoplasm. Loss of either C1orf109 or SPATA5 impairs global protein synthesis. These results link ribosome assembly with neurodevelopmental disorders associated with recessive SPATA5 mutations. Based on these findings, we propose that the expanded repertoire of ribosome biogenesis factors likely enables multicellular organisms to coordinate multiple steps of ribosome production in response to different developmental and environmental stimuli., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)